The present invention is directed to aqueous vehicles suitable for the parenteral administration of medicaments which are insoluble or only slightly soluble in water and pharmaceutical preparations incorporating such vehicles.
Vehicles known in the art for rendering insoluble or sparingly soluble medicaments suitable for parenteral administration utilize, generally, one or a mixture of synthetic solubilizing agents such as, for example, propylene glycol, polyethylene glycols, various emulsifying agents such as, for example, those marketed under the tradenames Cremophor EL, the Tweens and the Pluronics. The latter group of solubilizing agents functions by the formation of a colloidal system (micelles). The synthetic solubilizing agents including the above-mentioned micelle forming agents can be disadvantageous in that, upon parenteral administration, they may cause side effects such as, for example, allergic reactions, anaphylactic shock, hemolysis and pyrogenic action.
In addition to the synthetic micelle forming agents discussed above, there are available to the pharmaceutical compounder natural micelle forming agents such as, for example, cholic acid and various derivatives thereof. These natural micelle forming agents are, however, ionic and, therefore, strongly lytic. They produce hemolysis and have accordingly not previously been considered for compounding of preparations for parenteral administration.
It has been found in accordance with the present invention that the disadvantageous lytic action of the above-mentioned cholic acid derivatives can be substantially reduced or even eliminated by combining such micelle forming agents with certain lipoids. There is thus realized parenteral vehicles for insoluble or sparingly soluble medicaments which utilize as a micelle forming agent cholic acid and certain derivatives thereof not heretofore considered for use in parenteral preparations.